This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. People with Down Syndrome (DS) comprise a special population of individuals at risk for AD. In DS, the pathological changes of the brain are seen in childhood and accumulate across the lifespan (Lott and Head, 2001). The prevalence of dementia in DS varies from 13 to 75% increasing with age. The ADRC at UCI is unique among NIA funded Centers in having a sustained focus on DS as a special poulation susceptible to AD. Subjects in the DS cohort will be studied in parallel to subjects in the ADRC from the general population. The research design comprises the following: 1) Confirmation of dementia status, if present, by neurological and neuropsychological measures relevant to DS;2) Longitudinal follow-up;3) Collection and examination of the brain by post mortem protocols within the ADRC. This application is an extension of the IRB approved protocol for the ADRC (2001-1845).